Role of the sodium-calcium exchanger (NCX) in neuronal hypoxia and neuroprotection

The sodium calcium exchanger (NCX) is a membrane transporter, which is fundamental in Ca2+ intracellular homeostasis, because of its ability to move Ca2+ out or into the cell depending on the electrochemical gradient. NCX regulation is complex and not completely understood. There are three NCX isoforms, and all of them are involved in processes related to neuronal survival. In neurons exposed to hypoxia, the NCX inhibition increases neuronal death, instead NCX stimulation protects neurons from the hypoxic damage and reduces the infarct area in animal models. Molecules with the ability of stimulate selectively NCX have been developed and it could be the baseline for future neuroprotective strategies; however, further research is needed to better understand NCX regulation in physiological stress situations and its relevance in the mechanism of a number of agents that have been associated with neuroprotection or neurotoxicity. NCX is a potential therapeutic target on hypoxia conditions that requires more research to determine the effectiveness of its pharmacological handling; also, it is necessary to establish the importance that possess other Ca2+ transport mechanisms on the neuronal hypoxia, to develop clinically effective strategies of neuroprotection.